Background: Calcineurin-inhibitors (CNI) are used in renal transplant patients (RTX) to prevent rejection. CNI mainly suppress T-cell mediated immunity but very little is known about the impact of long-term treatment with CNI on T-cell function.

Objective: We investigated the immunological effects of long-term CNI intake in RTX patients in comparison to short-term CNI administration in healthy controls (HC).

Methods: Blood was drawn from 30 RTX patients with long-term CNI treatment. In addition, blood was sampled from HC with short-term CNI treatment (four dosages) before the first and 2 hours after the last CsA intake. T-cells were analyzed for cytokine production, proliferation, and CD25 expression.

Results: Short-term CNI reduced T-cell derived IL-2 and IFNγ as well as T-cell proliferation in HC. IFNγ was not suppressed in patients with long-term CNI treatment. IL-2 production, CD25 expression, and T-cell proliferation were enhanced in long-term CNI patients.

Conclusion: Suppression of IFNγ/IL-2 and T-cell proliferation is weaker during long-term CNI treatment in patients compared to short-term treatment in healthy subjects. Enhanced CD25 expression may lower the threshold for T-cell activation during long-term CNI treatment.

背景：钙调神经磷酸酶抑制剂 (CNI) 用于肾移植患者 (RTX) 以防止排斥。CNI 主要抑制 T 细胞介导的免疫，但对 CNI 长期治疗对 T 细胞功能的影响知之甚少。

目的：我们研究了 RTX 患者长期 CNI 摄入与健康对照 (HC) 短期 CNI 给药相比的免疫学影响。

方法：从 30 名长期接受 CNI 治疗的 RTX 患者中抽取血液。此外，在最后一次 CsA 摄入前的第一个和 2 小时之前，通过短期 CNI 治疗（四个剂量）从 HC 中采集血液样本。分析了 T 细胞的细胞因子产生、增殖和 CD25 表达。

结果：短期 CNI 减少了 T 细胞衍生的 IL-2 和 IFNγ 以及 HC 中的 T 细胞增殖。接受长期 CNI 治疗的患者中 IFNγ 并未受到抑制。长期 CNI 患者的 IL-2 产生、CD25 表达和 T 细胞增殖增强。

结论：与健康受试者的短期治疗相比，长期 CNI 治疗患者对 IFNγ/IL-2 和 T 细胞增殖的抑制较弱。增强的 CD25 表达可能会降低长期 CNI 治疗期间 T 细胞活化的阈值。